PROJECT SUMMARY Rabies has the highest case fatality rate of any known human infectious disease and kills around 59,000 people annually. Nearly all of these deaths (99%) occur in Africa and Asia and are due to canine rabies. While human rabies can be prevented with post-exposure prophylaxis (PEP), the intervention is costly and often not available in remote communities where it is needed. Targeting control efforts at the reservoir host through mass dog vaccination (MDV) is a socially equitable and effective approach. However, implementing MDV across the rural landscapes where rabies remains endemic is logistically challenging and, consequently, expensive. Moreover, there has only been limited empirical evidence to demonstrate the cost-effectiveness of MDV in achieving public health outcomes. As a result many countries spend substantial resources on provision of PEP with only limited investment in MDV. The goal of the proposed study is the elimination of dog-mediated human rabies, whilst the long term objective is the provision of cost-effective control strategies across the remote landscapes where rabies remains endemic. To achieve this a randomized controlled trial (RCT) will be carried out to compare vaccination coverage under two delivery strategies: the standard centralized team-led delivery (which is logistically challenging and results in irregular coverage, at cost) and a decentralized community-led approach (made possible through the recent determination that rabies vaccines are thermotolerant and can be stored for extended periods outside of refrigeration units) (Aim 1). The hypothesis is that community-led delivery will result in more consistent coverage at lower cost per dose. Second, an enhanced rabies surveillance network will be used to quantify the public health impact following the introduction of MDV in Aim 1 (Aim 2). Rabies incidence in the dog population is predicted to decline rapidly and public health impacts to accrue (fewer people bitten, less PEP required and fewer human deaths). Third, the outputs from Aims 1 and 2 will be used to model the impact that delivery strategy has on public health outcomes (Aim 3). The hypothesis is that community-led MDV delivery will result in improved public health outcomes and achieve elimination more rapidly than standard team-led MDV. Fourth, the outputs from Aims 1 ? 3 will be used to carry out a suite of cost-effectiveness and benefit-cost analyses to understand the cost-effectiveness and net benefits derived from the two MDV strategies. In quantifying the reduction in the human rabies burden that MDV provides and the comparative effectiveness and cost effectiveness of the delivery strategies, this study will provide much needed data that will inform international policy on the best approaches to eliminate rabies at scale. With a date of 2030 set by WHO/OIE/FAO for the global elimination of dog- mediated human rabies, the study?s outputs will provide a critical and timely contribution to guide elimination in canine- rabies endemic countries.